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10/31/2018

Biopharma/Investing
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Celgene is going to have a rough next decade. With 12 of 15 billion in revenue disappearing in the form of generic Revlimid, Otezla and Abraxane, I’m not sure CART, JAK and S1P1 will do the trick. The company spent a lot of money on buybacks and finds itself in a potent net debt position. Novartis reported $20m in revenue in the second full quarter of their CART product Kymriah. You know what to do!

Papers I’ve Read
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Mutant APP and Amyloid Beta-induced defective autophagy, mitophagy, mitochondrial structural and functional changes and synaptic damage in hippocampal neurons from Alzheimer’s Disease. Reddy et al. Hum Mol Genet 2018.
Papers like this should not be published. The authors find impaired mitochondria in AD neurons. No shit. Things go wrong, horribly wrong in Alzheimer’s brains. Biological processes are upended and synaptic integrity collapses. Why? Well, we know that mAPP (mutated amyloid precursor protein) patients suffer early-onset AD, which certainly implicates A-beta. Despite this, all attempts to neutralize A-beta have not changed outcomes in AD. This is probably due to a temporal-treatment mismatch. But this paper tries to suggest impaired mitophagy and mitochondrial function as a direct consequence of AB. It certainly is an epiphenomenon, but that is about all that can be claimed. Eating fruit in my home and then throwing it in the garbage results in garbage. Not throwing that garbage into the incinerator or leaving it on the sidewalk results in garbage buildup. Garbage buildup will attract rats. Rats crowding my kitchen garbage can will scare wifey. Wifey punching me in the face will cause a black eye. Eating fruit does not cause black eyes.

Brief Review – Ship of Fools – Tucker Carlson
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Liberals and the bi-curious should read this. Carlson provides the best current thinking from the right. He does not genuflect to Trump (and even seems dismayed), which perhaps is a conscious effort to win credibility from the reader, so don’t think you’re picking up a propaganda pamphlet. With his television charisma transported to the page, Carlson runs through a dozen or so disparate subjects through his perceptive and historically-informed lens. How left-core issues have become right-core issues (labor) fascinated me. I’m not a keen politics observer but I really enjoyed this as Carlson lauds certain old-line liberal principles (which appeal to me) and have been lost in today’s demagoguery.

Football
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The Bills play remarkably well for their record. Their defense made the Patriots look silly and I “sweated” this game substantially. I took the Patriots ML, -13.5 and a tiny bit -21.5. So, I was 3-0 this weekend (Patriots, Panthers, Redskins)! Now if I can only get my poker game moving… I’ll try to post football picks BEFORE the games start. With the return of the old PCs, I am attracted to writing again. I’m still very busy, however! Despite this I am also going to try and pay attention to basketball.

Poker
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Someone tried to play a constant all-in/rebuy game against me. That didn’t work. Taking blinds here and there and then getting slammed on AI calls was a quick lesson for villain.

Personal
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Thanks to my new friend who sent me works on Real Analysis, Topology and other fields. Math sits at the throne of the mind.

I appreciated your insights on the AD – A-beta – autophagy paper. I do want to express my sympathy for the authors. It can be hard to see the trees for the forest. When you have a lot of mechanistic explanations that evolve out of the numerous physiological manifestations it’s difficult to seperate whats consequential or causative within that cascade of events, often it can be both. But sometimes consequences can have theoretical importence but happen to contribute nothing to the disease process. Making it a dead end.

I wonder what book you are reading for poker. I have Sklansky “nolimit holdem” and chen and ankenman’s “mathematics of poker” unopened gathering dust on my bookshelf. probably going to stay that way unless i get locked up myself

I agree with the idea that liberal side has gone crazy left but the Republicans and Trump in power are currently more dangerous. He’s literally giving speeches saying he wants to kill people and start concentration camps. I’d like to get Trumpism out of the way, but I think the radicalized left is making things worse.

I just wish there was a voice of reason in politics and right now. I’m just so disfranchised and getting apathetic about the whole thing because no one seems to want to actually fix anything.

When? Again they’re not the ones in power. Trump and the Republicans are and Trump literally encourages and tells people at his rallies to be violent. A couple people as of recently took this guy seriously and sent bombs to people. They all used Trump’s talking points.

How do you know so much about bio and science in general? Didn’t you study business? How did you learn all of this about biotech, bio, chem, literally all this stuff? Can someone recommend me some resources for learning this stuff as well? Teach me your ways..

How did you learn so much about so many different things like Biology, Chemistry, Statistics, etc? I think you studied business administration. How can I also learn these things without going to school for them? If anyone else on here has any advice, please chime in too. I saw a guy above was diving into a chemistry textbook. Did you just read books about stuff you’re interested in to get to this point of expertise? Thanks.

Celgene’s rough decade is rough for Celgene but kinda funny to the rest of us because Bob Hugin’s entire campaign was centered around his ability to bring Celgene out of the gutters and transform it into a multi-million dollar company, but now Celgene is in the gutters once again … whomp whomp. Fingers crossed for Bob Hugin tho.